CELL-TYPE-SPECIFIC INTERACTIONS BETWEEN RETINOIC ACID AND THYROID-HORMONE IN THE REGULATION OF EXPRESSION OF THE GENE ENCODING ORNITHINE AMINOTRANSFERASE

The purposes of this study were to determine whether expression of the gene encoding ornithine aminotransferase (OAT) in the rat liver and k idney is regulated by retinoic acid (RA) and to characterize further t he role of thyroid hormone in regulating the expression of this gene. The level of OAT messenger RNA (mRNA) was reduced 70% in the Liver of animals fed a vitamin A-deficient diet relative to that in animals fed a vitamin A-sufficient diet. RA, administered at a dose of 20 mu g/ra t to A-deficient rats for 1 or 3 days, restored OAT mRNA to near the l evel observed in animals fed the A-sufficient diet. Retinol was also e ffective in this regard. T-3, when injected alone at a dose of 10 mu g /100 g BW, had no effect on the level of OAT mRNA in the liver. Howeve r, when injected concurrently with RA, T-3 blocked the ability of RA t o induce OAT mRNA in the liver of rats fed the vitamin A-deficient die t. Animals made both vitamin A deficient and hypothyroid responded to RA in a manner similar to vitamin A-deficient animals. The vitamin A-d eficient, hypothyroid rats responded somewhat differently to T-3, howe ver. T-3 was unable to block the induction of OAT mRNA in the liver of vitamin A-deficient, hypothyroid rats when injected concurrently with RA for 1 day, but did block the induction of OAT mRNA by RA when thes e two hormones were injected concurrently for 3 days. These data indic ate that RA and T-3 exert opposing effects on the level of OAT mRNA in the liver. The effects of RA and T-3 on OAT mRNA were markedly differ ent in the kidney. Neither vitamin A deficiency nor RA had any apparen t affect on the level of OAT mRNA in the kidney. T-3, however, increas ed the level of OAT mRNA in the kidney of vitamin A-deficient rats. In the kidney of vitamin A-deficient, hypothyroid rats, T-3 was unable t o increase OAT mRNA when injected for 3 day, but did increase this mRN A when injected for 3 days. Together, these data indicate cell-type sp ecific effects of bath RA and T-3 on the OAT gene.